Fig. 4.

Multi-functions of E3 ligases. Based on the different E3 ligases and their specific substrates, E3 ligases can involve in many different cellular progression such as proliferation, apoptosis, DNA damage repair, immunity and metabolism. We have shown some E3 ligases mentioned in this review and how they function in regulating cancer cell progression. For example, the E3 ligases FBXW7, HECTD3, CUL3/SPOP/RBX1, Parkin, SKP2 are involved in regulating proliferation or apoptosis through targeting proliferation-associated proteins for ubiquitination. E3 ligases HUWE1, RNF126, RNF138 are shown to regulate cancer cell DNA damage repair by targeting specific substrates for ubiquitination. E3 ligases FBXO38, KLHL22, TRIM25, RNF2 regulate cancer cell immune response through promoting ubiquitination of specific substrates. And E3 ligases PPARγ, SKP2, CHIP, VHL, TRAF6, HUEW1,MuRF1 are capable of mediating cancer cell metabolism by targeting related substrates for ubiquitination. Note:we use different background colors to distinguish each E3 ligases. Blue background represents the genes they target for degradation and pink background represnets genes they target for stabilization or others but not degradation. We use × to show the disruption of protein-protein interaction